The aims of this project are 1) to study the mechanisms of microtubule assembly and their control and 2) to use this knowledge to further our understanding of the role of microtubules in immunologic processes, particularly, immediate and delayed hypersensitivity. Initial experiments will involve the study of microtubule assembly in cell-free preparations, i.e., partially purified microtubule protein prepared, initially at least, from brain. The aims of this part of the project are 1) to eluciate the nature of the assembly process and 2) to determine the effects of drugs and other agents on the assembly process. Particular emphasis will be placed on the relationship of cyclic AMP, a compound of known importance in immediate and delayed hypersensitivity to microtubules. Subsequent experimentation will involve a developed in vitro model of immediate hypersensitivity: antigen induced, IgE-mediated histamine release from human leukocytes (basophils). The aim of this part of the project is to apply the knowledge gained from the study of the purified microtubule system to further define the role of microtubules in immediate hypersensitivity and to control the process at the level of the microtubule system. While emphasis will be placed on immediate hypersensitivity, it is clear that the microtubule system is also important in other immunological processes, e.g., delayed hypersensitivity. As warranted by the progress of the study, experiments will also be carried out therefore with an in vitro model of delayed hypersensitivity: target cell (mastocytoma) destruction (Cr51 release) by sensitized allogeni mouse splenic lymphocytes. The long term goal of this project is the prevention or the connrol of the symptoms of immediate hypersensitivity through control of the function of the microtubule system.